Spray-Dried Nanoparticles-in-Microparticles System (NiMS) of Acetazolamide Using Central Composite Design

In the present study, spray-dried nanoparticles-in-microparticles system (NiMS) of Acetazolamide (ACZ) was formulated for preparing orally disintegrating tablets (ODT). The objective behind the study was to investigate the effect of - concentration of chitosan (X₁), volume of sodium tripolyphosphate (NaTPP) (X2) and inlet temperature of spray dryer (X₃) on entrapment efficiency of ACZ using Central Composite Design (CCD). The spray dried optimized NiMS were formulated into orally disintegrating tablets using direct compression method. It was found that batch NiMS-7 (formulated using 0.5 % w/v chitosan; 20 ml NaTPP at inlet temperature of 140ºC) has a maximum entrapment efficiency 56.08% (w/w), loading capacity 68.39% (w/w), percentage yield 30.15%, (w/w) and particle size of 455 nm. Analysis of Variance (ANOVA) was applied on the entrapment efficiency of NiMS to study the fitting and the significance of the model. The estimated model may be further utilized as response surface for entrapment efficiency of NiMS. The batch NiMS-7 showed 90.70% drug release after three hours in phosphate buffer pH 7.4 and 61.52% in 0.1 N HCl. Infrared analysis of NiMS-7 showed no interaction between drug and polymer during the formulation process. The optimized batch was further formulated into ODT. The ODT was formulated using sodium starch glycolate (52.5 mg), microcrystalline cellulose (15 mg), lactose (34.5 mg), mannitol (15 mg), talc (1.50 mg) and magnesium stearate (1.50 mg). The formulated ODTs have a disintegration time of 38 seconds. The hardness, friability and weight variation of ODTs were found to be within pharmacopoeial limits. In vitro drug release studies revealed that cumulative percent of drug released was found to be 92.90% in 60 mins and the release data followed the first order kinetics. Therefore, this NiMS approach has been successfully applied to formulate ODT of ACZ and can be advantageous for the treatment of glaucoma in the case of paediatric patients.

http://ift.tt/2bXwMfn


http://ift.tt/2cQrMjc